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Biomedical subjects

P Dombernowsky

Publications and source records attributed to P Dombernowsky.

At least 109 records · Page 6Linked to original sources
PubMed1991

Teniposide and etoposide in previously untreated small-cell lung cancer: a randomized study.

A randomized study comparing teniposide (VM-26) and etoposide (VP-16) was performed to investigate whether there are any differences in the activity and toxicity of these two analogs in small-cell lung cancer (SCLC). Only previously untreated patients with SCLC were included; 46 and 48 patients receiving VP-16 and VM-26, respectively, are assessable for response. There were no differences between the two groups with respect to extent of disease, median age, and performance status (PS). The initial doses were for both compounds 70 mg/m2 intravenously (IV) daily for 5 days every 3 weeks. After inclusion of 25 patients in the study, the doses were increased to 80 mg/m2 for VM-26 and 90 mg/m2 for VP-16 because of differences in toxicity. VM-26 caused more hematologic toxicity than VP-16 throughout the study. The overall responses (complete response [CR] plus partial response [PR]) were 65% for VP-16 and 71% for VM-26, with CR occurring in 24% and 23%, respectively, for the two compounds. Median survival was 8.5 months for VP-16-treated patients versus 11.3 months for VM-26-treated patients (P = .58). It is concluded that both VP-16 and VM-26 are highly active single agents in SCLC.

Aged↗
PubMed1990

[Sarcoma treatment in Denmark].

Approximately 240 sarcomas are registered annually in Denmark. Of these, 5/6 are soft-tissue sarcomas while the remainder consist of various types of sarcomas of bone. Determination of the histogenetic type, the degree of aplasia and the anatomical spread of the primary tumour is decisive for optimal prognostic assessment and for planning of the primary local treatment. The surgical treatment is aimed at radical treatment and, where tumours in extremities are concerned, this frequently involves reconstruction with endoprostheses with the object of salvaging the limb. Irradiation is indicated in cases of soft-tissue sarcoma which are not amenable to radical operation and as palliative treatment. In cases of soft-tissue sarcoma, cytostatic therapy with adriamycin alone or combined with iphosphamide in metastasizing disease can result in response in 30-50% of the patients. On the other hand, the value of adjuvant treatment is not yet elucidated. In cases of osteogenic sarcoma, the data available at present suggest that prolongation of the survival rate may be obtained by means of intensive adjuvant cytostatic treatment, but the optimal regimen is not yet defined. In other situations, cytostatic therapy must be considered as experimental and not indicated outside the fields of controlled investigations. Optimal diagnosis and treatment of sarcoma requires extensive multidisciplinary contributions which should be centralized in the fewest possible centres. Intimate national and international cooperation is also essential.

Antineoplastic Agents↗
PubMed1990

Phase II study of teniposide in advanced breast cancer.

In a phase II study, 19 patients with previously treated, advanced breast cancer received 50 mg/m2 teniposide (VM-26) i.v. on days 1-5 every 3 weeks. One partial response (PR) (5%) was observed. Toxicity consisting of leukopenia and thrombocytopenia was frequent and severe. VM-26 has minimal therapeutic activity when given at this dose and on this schedule to patients with heavily pretreated metastatic breast cancer.

Adult↗
PubMed1990

Comparison of the effect of cortisol on aromatase activity and androgen metabolism in two human fibroblast cell lines derived from the same individual.

The effect of preincubation with cortisol on estrogen and androgen metabolism was investigated in human fibroblast monolayers grown from biopsies of genital and non-genital skin of the same person. The activity in the cells of aromatase, 5 alpha-reductase, 17 beta-hydroxysteroid oxidoreductase and 3 alpha-hydroxysteroid oxidoreductase was investigated by isolating estrone, estradiol, estriol, dihydrotestosterone, androstanedione, androsterone, 3 alpha-androstanediol, testosterone and androstenedione after incubation of the cells with [14C]testosterone or [14C]androstenedione. For experiments with 14C-labeled substrate the cells were incubated in medium, charcoal stripped of steroids without Phenol Red. Preincubation from 6 to 36 h with cortisol in concentrations of 10(-8) - 10(-6) M showed maximal stimulation of aromatase activity after 12 h preincubation with cortisol in concentrations of 0.5-1.0 x 10(-6) M in both cell lines. When preincubation with cortisol was omitted no estrogen synthesis was detected. The formation of androgen was not altered after preincubation with cortisol. Pronounced differences were found in estrogen and in androgen metabolism in the two cell lines suggesting a local regulation of the hormonal environment. The aromatase activity, which is low in many tissues could be stimulated by cortisol without altering the androgen metabolism was found to be a suitable system for investigations of the cellular interconversion of androgens and estrogens and for investigations of the in vitro regulation of the enzymes involved.

Androgens↗
PubMed1990

The limited value of routine chest X-ray in the follow-up of stage II breast cancer.

In 280 patients with stage II breast cancer, chest X-ray was performed at 6 and 12 months and yearly thereafter to the 6th year or until recurrence, another cancer was detected, the patient refused further follow-up or died. Among 1289 scheduled chest X-rays, malignant changes were found in 20 patients, of which only 3 had pulmonary symptoms. In a further 14 patients malignant changes were suspected, but follow-up examinations could not prove malignancy. 26 patients presented within 12 months after the last scheduled X-ray with pulmonary symptoms and a work-up chest X-ray revealed malignant changes. Thus, in only 1.3% of the scheduled X-rays were unsuspected malignant changes diagnosed. Median survival of patients with malignant chest X-rays found at scheduled controls versus between scheduled controls did not differ significantly (P = 0.26). It is concluded that routine chest X-ray is not indicated in patients with stage II breast cancer.

Adult↗
PubMed1990

Ifosfamide plus doxorubicin in previously untreated patients with advanced soft tissue sarcoma. The EORTC Soft Tissue and Bone Sarcoma Group.

The objective of this phase II trial was to assess the therapeutic activity and toxicity of doxorubicin plus ifosfamide in previously untreated patients with advanced soft tissue sarcoma. Treatment was doxorubicin 50 mg/m2 followed by a 24 h infusion of ifosfamide 5 g/m2 plus mesna 2.5 g/m2 repeated every 3 weeks until disease progression or unacceptable toxicity occurred. Of 203 patients entered, 175 were evaluable for response. The response rate was 35% (95% CI 28-42%), with 9% of the patients achieving a complete remission and 26% a partial remission. The median time to progression was 29 weeks for all evaluable patients, and 67, 40 and 28 weeks for complete and partial responders and patients with stable disease, respectively. The median duration of survival was 58 weeks. Myelosuppression was the dose-limiting toxicity, resulting in leukopenia (WHO grade 3 and 4) in 73% of evaluable treatment courses. Other side-effects were rare and usually well manageable.

Adolescent↗
PubMed1990

Epirubicin or epirubicin and vindesine in advanced breast cancer. A phase III study.

One hundred thirty-three evaluable patients with advanced breast cancer entered a randomized trial comparing epirubicin 60 mg/m2 with a combination of epirubicin 45 mg/m2 and vindesine 3 mg/m2 day 1 and 8 every 4 weeks. In all 10 premenopausal women an oophorectomy was performed. Seventy-five patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for advanced disease and 68 had received adjuvant chemotherapy (cyclophosphamide or CMF). Among evaluable patients (72 in the epirubicin group and 61 in the epirubicin + vindesine group) response rates were as follows: complete response--seven versus six; partial response--31 versus 22; no change--16 versus 17 (p greater than 0.40). Median time to disease progression was 6 months in both groups and median survival times were identical (12 months). Thrombocytopenia was less frequent in the epirubicin + vindesine group (p less than 0.01). In the epirubicin + vindesine group, mild to moderate peripheral neuropathy was observed in 40% of the patients. Congestive heart failure developed in one patient with a cumulative dose of epirubicin less than 1000 mg/m2 and in 7 of 15 patients who had greater than 1000 mg/m2. Four died of this cause. In conclusion, epirubicin is effective as a single agent for advanced breast cancer. The combination with vindesine does not increase its efficacy.

Adult↗
PubMed1990

TCNU in adenocarcinoma of the lung: a phase II study with divided doses.

TCNU, a new water soluble nitrosourea, has in preclinical studies shown higher activity when given as divided doses compared with one day single treatment. Accordingly, 38 consecutive patients with non-resectable adenocarcinoma of the lung received TCNU 40 mg/m2 p.o. daily for three days every 4 weeks. The response rate among 37 evaluable patients was 14%, median response duration was 17 weeks (range 5-57+ weeks) and median survival 22 weeks (range 3-96+ weeks). Hematologic toxicity was pronounced, especially thrombocytopenia, and 57% of the patients had WHO grade 3 or 4 WBC or platelet count. Overall, dose reduction or delay of treatment due to hematologic toxicity was necessary in 66% of the patients. This, together with the limited activity, renders TCNU in the present dose and schedule unsuitable for further investigations in this disease entity.

Adenocarcinoma↗
PubMed1990

Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer.

The cardiotoxicity of epirubicin (EPI) was evaluated clinically, radiologically, with ECG, and with multiple ECG-gated radionuclide determination of the left ventricular ejection fraction (LVEF) during rest in 135 patients with advanced breast cancer. The EPI doses were 60 mg/m2 on days 1 and 8 every 4 weeks or 45 mg/m2 plus vindesine 3 mg/m2 on the same schedule. The median cumulative dose of EPI was 500 mg/m2 (range, 47 to 1,563). Eight of the 135 patients developed congestive heart failure (CHF). Of 67 patients treated with EPI less than 500 mg/m2, none developed CHF. Among 48 patients treated with doses between 500 and 1,000 mg/m2, one had CHF (2%; 95% confidence limits, 0.1 to 11.1). Among 20 patients who received EPI from 1,000 to 1,563 mg/m2, seven developed CHF (35%; 95% confidence limits, 15.4 to 59.2). Four patients died due to cardiotoxicity. The risk of EPI cardiotoxicity at the present schedule is considerable at doses above 1,000 mg/m2. At doses between 500 and 1,000 mg/m2 the risk of CHF decreases, and at doses below 500 mg/m2, it is negligible. For all patients, the prevalence of CHF was 6% and the sensitivity of LVEF high (95%), mainly due to the low incidence of CHF. Among the 20 patients who received EPI at more than 1,000 mg/m2, the prevalence of CHF was 35% and the sensitivity only 64%. The specificity was maximally 62%. Our results suggest that LVEF is of no value as a predictor for CHF.

Adult↗
PubMed1989

Prospective evaluation of chronic cardiotoxicity due to high-dose epirubicin or combination chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil.

In a prospective study the left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), systolic blood pressure, ECG, and heart rate were recorded at rest and during submaximal work to compare the cardiotoxic effect of epirubicin with a combination chemotherapy without known cardiotoxicity. A total of 14 females with advanced breast cancer were treated with epirubicin at a median cumulative dose of 827 mg/m2 (range, 550-1244). These patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide alone as adjuvant treatment, or CMF for advanced disease. The control group consisted of 11 females with advanced breast cancer given CMF only. The systolic blood pressure at rest as well as during submaximal work was significantly lower (P less than 0.05) after treatment in the epirubicin group than in the CMF controls. With regard to LVEF, the median value of 54% at rest was significantly lower after treatment in the epirubicin group than in the controls (59%). There was a significant fall in LVEF at rest and during exercise in the epirubicin group, whereas no such changes were found in the CMF controls after treatment. The RVEF was unaffected. In the epirubicin-treated group one patient developed fatal congestive heart failure, and in the remaining 13 patients treatment was discontinued due to progression of the cancer and not to cardiotoxicity. Thus, the cardiotoxicity of epirubicin changed the clinical outcome in only 1 of 14 patients with advanced breast cancer.

Adult↗
PubMed1989

The value of yearly chest X-ray in patients with stage I breast cancer.

In 263 patients with stage I breast cancer, i.e. tumour less than 5 cm in diameter, no invasion of skin and deep fascia, and no involvement of axillary lymph nodes, X-rays of the chest were performed at 6, 12 months and yearly thereafter to the 6th year or until recurrence, another cancer was detected, the patient refused further follow-up or died. Among 1599 examinations, in only 0.25% (four patients) were unsuspected malignant changes observed. Due to this low cost/benefit ratio a fixed routine schedule of repeated chest X-rays in stage I cancer patients, otherwise apparently free of disease, is not justified.

Breast Neoplasms↗
PubMed1989

Creatine kinase-BB in the cerebrospinal fluid as a marker of CNS metastases and leptomeningeal carcinomatosis in patients with breast cancer.

To determine whether creatine kinase-BB isoenzyme would be useful in detecting central nervous system metastases secondary to breast cancer, we measured the cerebrospinal fluid (CSF) activity of creatine kinase (CK) and its BB isoenzyme (CK-BB) in 65 consecutive patients suspected of having CNS involvement. All patients underwent neurological evaluation, computer tomography (CT) scan and/or radionuclide scintigraphy and lumbar puncture with CSF examination. Thirty patients had CNS metastases, of whom 18 had parenchymal brain metastases (MET). Twelve had leptomeningeal carcinomatosis (MC), of whom four also had parenchymal brain metastases. Thirty-four patients were concluded not to have CNS involvement, whereas one was considered equivocal. CK-BB activity was significantly higher in patients with CNS metastases than in those without (P less than 0.05). This difference was primarily related to the fact that patients with MC had a significantly higher CK-BB activity than patients without CNS metastases or patients with parenchymal brain metastases only (P less than 0.01 and P less than 0.05, respectively). Taking 0.20 U/l as a tentative cut-off value (the upper limit range of patients without CNS metastases being 0.19 U/l), 10 out of 12 patients with MC had activities above this level. The sensitivity and specificity for having MC were 83% and 87%, and the positive and negative predictive values 60% and 96%, respectively. The sensitivity and negative predictive value for having any CNS metastases were 57% and 72%. Specificity and positive predictive value: 100%. The CSF activity of CK-BB appears to be a contribution in the diagnosis of MC secondary to breast cancer and seems superior to protein and LDH.

Biomarkers, Tumor↗
PubMed1989

TCNU (LS 2667), a new active drug in the treatment of advanced colorectal cancer. EORTC Early Clinical Trials Group.

Fifty-seven patients with advanced measurable or evaluable colorectal cancer not previously treated with chemotherapy and tumor manifestations from colorectal cancer were treated with tauromustine (TCNU), a new nitrosourea with a therapeutic index against murine tumors better to or equal to that of the established nitrosoureas. The dose was 130 mg/m2 orally q 5 weeks. There were one CR and seven PR, for an overall response rate of 14%. Responding sites included the liver (one CR and two PR), lung (four PR) and lymph nodes (two PR). The median duration of response was 33+ weeks (21+ to 34 weeks). The main dose limiting toxicity was myelosuppression which seemed to be cumulative. Subjectively, the drug was well tolerated although most patients experienced nausea and vomiting for some hours. It is concluded that TCNU is a well tolerated compound with limited, but definite antitumor activity against colorectal cancer and that further studies in this disease could be of interest.

Adenocarcinoma↗
PubMed1989

Significance of incisional biopsy in breast carcinoma: results from a clinical trial with intended excisional biopsy.

The recurrence-free survival rates (RFS) after one-stage mastectomy and partial axillary dissection in 1242 low risk breast cancer patients with invasive ductal carcinoma with or without residual cancer tissue (RCT) in the wall of the biopsy cavity were compared. RFS was significantly lower in patients with RCT (RCT-positive) whether premenopausal (n = 416) or postmenopausal (n = 826). By applying the Cox multivariate analysis on RCT and various known prognostic criteria, the incidence rates for RCT-positive patients relative to RCT-negative patients were estimated. The relative risk by RCT-positivity was in the order of 1.45, indicating that RCT is an independent risk factor contributing an increased risk of recurrence of about 45%.

Axilla↗